Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study.

OBJECTIVE: To investigate the occurrence of olfactory and gustatory dysfunctions in patients with laboratory-confirmed COVID-19 infection. METHODS: Patients with laboratory-confirmed COVID-19 infection were recruited from 12 European hospitals. The following epidemiological and clinical outcomes have been studied: age, sex, ethnicity, comorbidities, and general and otolaryngological symptoms. Patients completed olfactory and gustatory questionnaires based on the smell and taste component of the National Health and Nutrition Examination Survey, and the short version of the Questionnaire of Olfactory Disorders-Negative Statements (sQOD-NS). RESULTS: A total of 417 mild-to-moderate COVID-19 patients completed the study (263 females). The most prevalent general symptoms consisted of cough, myalgia, and loss of appetite. Face pain and nasal obstruction were the most disease-related otolaryngological symptoms. 85.6% and 88.0% of patients reported olfactory and gustatory dysfunctions, respectively. There was a significant association between both disorders (p < 0.001). Olfactory dysfunction (OD) appeared before the other symptoms in 11.8% of cases. The sQO-NS scores were significantly lower in patients with anosmia compared with normosmic or hyposmic individuals (p = 0.001). Among the 18.2% of patients without nasal obstruction or rhinorrhea, 79.7% were hyposmic or anosmic. The early olfactory recovery rate was 44.0%. Females were significantly more affected by olfactory and gustatory dysfunctions than males (p = 0.001). CONCLUSION: Olfactory and gustatory disorders are prevalent symptoms in European COVID-19 patients, who may not have nasal symptoms. The sudden anosmia or ageusia need to be recognized by the international scientific community as important symptoms of the COVID-19 infection.

Psychological Distress in a Sample of Adult Italian Patients Affected by Vocal Nodules and Muscle-Tension Dysphonia: Preliminary Results.

OBJECTIVES: To evaluate the correlation between voice disorders and psychological distress, in terms of anxiety, stress, and depression, in a sample of adult Italian patients and to compare our results with those obtained in a group of adult healthy controls matched by age, sex, geographic distribution, and occupation. METHODS: This prospective-controlled study included 100 adults with Vocal nodules (VN) and Muscle Tension Dysphonia (MTD1), aged between 18 and 65 years, as Experimental Group (EG) and 100 age-matched subjects without any voice disorders as a Control Group (CG). All patients in the EG underwent a phoniatric evaluation, including the administration of the Voice Handicap Index (VHI) and laryngeal examination. Both patients of EG and CG underwent a Psychological evaluation by means of standardized tests; Beck's Depression Inventory, State Anxiety Inventory (STAI 1-State Anxiety), Trait Anxiety Inventory (STAI 2- Trait Anxiety), and Perceived Stress Scale (PSS-10) were completed by patients. Fisher's exact test and chi-squared test were used to compare all categorical variables, whereas numerical variables were compared either with the nonparametric Mann-Whitney-Wilcoxon or with Kruskal Wallis test. General linear models were used to study continuous variables between patients and controls and between different groups within the sample. RESULTS: In the study group, the Physical domain (P score) of the VHI was more affected than the Emotional (E score) and Functional ones (F score) both in patients with MTD1 and VN; patients with VN presented a significant difference in P score, E score and VHI total score than patients with isolated MTD 1 (P < 0.005). Psychological assessment showed a significant difference (P < 0.005) between VN and MTD 1 regarding PSS-10 and STAI-1 scores. Low Beck's Depression Inventory scores were present in our sample without significant differences between patients with VN and those with MTD 1. Scores related to psychological distress in the EG were far superior to those obtained by the healthy CG, with markedly significant values especially for PSS-10 (P < 0.0001) and STAI 2 (P < 0.01). Finally, younger patients (18-35 years) with VN showed a highest risk of psychosocial distress. CONCLUSION: the present study identified a high prevalence of psychological distress among patients with vocal disorders without any prior specific psychiatric diagnosis, especially in terms of anxiety and perceived stress. For this reason both these symptoms should be taken into consideration in the diagnostic, therapeutic, and follow-up process of patients with MTD1 and VN.

Ipecac root extracts and isolated circular peptides differentially suppress inflammatory immune response characterised by proliferation, activation and degranulation capacity of human lymphocytes in vitro.

Circular peptides are attractive lead compounds for drug development; this study investigates the immunomodulatory effects of defined root powder extracts and isolated peptides (called cyclotides) from Carapichea ipecacuanha (Brot.) L. Andersson ('ipecac'). Changes in the viability, proliferation and function of activated human primary T cells were analysed using flow cytometry-based assays. Three distinct peptide-enriched extracts of pulverised ipecac root material were prepared via C18 solid-phase extraction and analysed by reversed-phase HPLC and mass spectrometry. These extracts induced caspase 3/7 dependent apoptosis, thus leading to a suppressed proliferation of activated T cells and a reduction of the number of cells in the G2 phase. Furthermore, the stimulated T cells had a lower activation potential and a reduced degranulation capacity after treatment with ipecac extracts. Six different cyclotides were isolated from C. ipecacuanha and an T cell proliferation inhibiting effect was determined. Furthermore, the degranulation capacity of the T cells was diminished specifically by some cyclotides. In contrast to kalata B1 and its analog T20K, secretion of IL-2 and IFN- γ was not affected by any of the caripe cyclotides. The findings add to our increased understanding of the immunomodulating effects of cyclotides, and may provide a basis for the use of ipecac extracts for immunomodulation in conditions associated with an exessive immune responses.

Boswellia carteri extract and 3-O-acetyl-alpha-boswellic acid suppress T cell function.

Resins from various Boswellia species have a long track record in different cultures as a treatment for inflammatory diseases. This study was designed to provide evidence for the anti-inflammatory capacity and medicinal use of Boswellia carteri (Burseraceae). A dichloromethane (DCM) extract of B. carteri gum resin and isolated compounds thereof were immunologically characterized. Flow cytometric-based analysis was performed to investigate the impact of B. carteri extract on proliferation, viability, and function of anti-CD3 and anti-CD28 activated human primary T cells. The secretion level of IL-2 and IFN-γ was determined by a bead array-based flow cytometric technique. HPLC-based activity profiling of the B. carteri extract identified active compounds. The impact of B. carteri extract and isolated compounds on the IL-2 transcription factor activity was addressed using specially designed Jurkat reporter cells. The extract of B. carteri suppressed the proliferation of human primary T lymphocytes in vitro in a concentration-dependent manner, without inducing cytotoxicity. Thereby, the B. carteri extract further reduced the degranulation capacity and cytokine secretion of stimulated human T cells. Transcription factor analysis showed that the immunosuppressive effects of the extract are based on specific NFAT-conditioned suppression within T cell signaling. Through HPLC-based activity profiling of the extract, 3-O-acetyl-alpha-boswellic acid was identified as the compound responsible for the NFAT-based mechanism. The recent study presents a scientific base for the immunosuppressive effects of B. carteri gum resin extract including a mode-of-action via the NFAT-conditioned suppression of T lymphocyte proliferation. The immunosuppressive effects of 3-O-acetyl-alpha-boswellic acid are depicted for the first time.

Influence of traditionally used Nepalese plants on wound healing and immunological properties using primary human cells in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: The improvement of wound healing has always been an important issue for both ethnopharmacological and modern medical research. In this study, we used state-of-the-art methods to investigate extracts of plants used traditionally in Nepal for more than 1000 years to treat inflammatory injuries. AIM OF THE STUDY: We focused on the potential of the plant extracts to ameliorate wound healing and to influence immune modulatory properties. MATERIALS AND METHODS: Nine Nepalese plant extracts in three different solvents (methanol, ethyl acetate, petroleum ether) were immunologically characterised. Water-soluble tetrazolium (WST-1) assays and scratch assays were performed to determine their impact on viability and wound healing capacity of human keratinocytes and fibroblasts. Effects on proliferation, viability and function of physiologically relevant anti-CD3 and anti-CD28 stimulated primary human T lymphocytes were assessed using carboxyfluorescein succinimidyl ester (CFSE), annexin V/propidium iodide staining assays and flow cytometry-based surface receptor characterisation. The secretion level of interleukin-2 (IL-2) was analysed with the ELISA technique. Dendritic cells were generated out of peripheral blood mononuclear cells (PBMC) by CD14+ magnetic bead selection. Flow cytometry-based surface receptor characterisation and ELISA-based technique were used to evaluate the DC activation state and the interleukin-8 (IL-8) secretion level. RESULTS: We demonstrate that an ethyl acetate extract of Bassia longifolia and of Gmelina arborea have anti-inflammatory capacities, indicated by reduced proliferation, inhibition of IL-2 secretion and degranulation capacity of activated human T cells, when compared with adequate concentrations of synthetic positive drug controls. Furthermore, Gmelina arborea improved the wound healing of keratinocytes and fibroblasts and has tendency to increase the secretion of IL-8 by human primary dendritic cells. CONCLUSION: With this preliminary screening, we offer a scientific basis for the immunomodulatory properties of the two Nepalese medicinal plants Bassia longifolia and Gmelina arborea. However, further detailed studies regarding the responsible compounds are necessary.